Family physician views about primary care reform in Ontario: a postal questionnaire

Background  

Primary care reform initiatives in Ontario are proceeding with little information about the views of practicing family physicians.     

茶碱对有呼吸窘迫综合征的极早产儿患血管运动性肾病的预防作用研究：一项随机双盲安慰剂对照试验

背景:血管运动性肾病是早产儿常见的肾功能障碍性疾患。目的:确定茶碱是否可以预防有呼吸窘迫综合征的极早产儿罹患血管运动性肾病。方法:随机双盲安慰剂对照试验,50例胎龄≤32周须辅助通气的早产儿。婴儿接受3d茶碱(1m g/kg)或安慰剂静脉注射。每天测定其24h尿量。在第2、第5及第11天,收集血样及12h尿并进行电解质、肌酐、尿素分析。结果:茶碱组患儿的第1天排尿量的组别x(s)为2.4(0.9)m l/(kg·h),显著高于安慰剂组[1.6(1.0)m l/(kg·h);P=0.023]。茶碱组少尿或无尿的发生率(5%)显著低于安慰剂组(33%)。在第一次给予茶碱/安慰剂后24h,茶碱…     

Permeability of porcine blood brain barrier to somatostatin analogues

1. Transport of a fluorescent somatostatin analogue (NBD-octreotide) across freshly isolated functionally intact capillaries from porcine brain was visualized by confocal microscopy and quantitated by image analysis. 2. Luminal accumulation of NBD-octreotide showed all characteristics of specific and energy-dependent transport. Steady-state luminal fluorescence averaged 2 - 3 times cellular fluorescence and was reduced to cellular levels when metabolism was inhibited by NaCN. 3. The accumulation of NBD-octreotide in capillary lumens was inhibited in a concentration-dependent manner by unlabelled octreotide, by verapamil, PSC-833 and cyclosporin A, potent inhibitors of p-glycoprotein, and by leucotriene C(4), a strong modulator of Mrp2. Conversely, unlabelled octreotide reduced luminal accumulation of fluorescent BODIPY-verapamil on p-glycoprotein and of fluorescein-methotrexate, on Mrp2. None of the inhibitors used significantly reduced cellular accumulation of the fluorescent substrates. 4. Together, the data are consistent with octreotide being transported across the luminal membrane of porcine brain capillaries by both P-gp and Mrp2, providing further evidence that both transporters contribute substantially to the active barrier function of this endothelium.     

Parvovirus: the expanding spectrum of disease

Treatment of parvovirus infections among immunocompromised hosts using immunoglobulin has provided the clinician with a useful therapeutic tool but has also highlighted the problems concerning chronic disease states. The discovery of the human parvovirus B19 in 1975 and subsequent studies of its effects in humans have identified this virus as the causative agent of a broad spectrum of diseases. Recent improvements regarding the development of sensitive PCR techniques and methods for cultivation have provided new insight into its pathogenic role, its virology and immunology, and the varied clinical manifestations. The current state of knowledge concerning parvovirus enabled us to divide the long list of diseases caused by this virus into three main categories: (1) diseases found among normal hosts (asymptomatic disease, erythema infectiosum, arthropathy, hydrops fetalis), (2) hematologic diseases (aplastic crisis, chronic anemia, idiopathic thrombocytopenic purpura, transient erythroblastopenia of childhood, Diamond-Blackfan anemia) and, finally, (3) a heterogeneous group of diseases, in which the etiologic role of parvovirus is less clear and sometimes putative (neurologic disease, rheumatologic disease, vasculitic and myocarditic syndromes). In particular, arthropathy, hydrops fetalis and the hematologic disorders may be of pediatric concern. Consequently, it is of paramount importance that in all of these cases the clinician includes parvovirus as a differential diagnosis.     

Atherosclerosis in APOE*3-Leiden transgenic mice: from proliferative to atheromatous stage

BACKGROUND: This study documents (1) the progression of atherosclerosis along the entire arterial tree in APOE*3-Leiden mice after 1, 4, 6, 9, and 12 months of a high-fat/high-cholesterol (HFC) diet and (2) the amount and phenotype of DNA-synthesizing and apoptotic cells in different lesion types after 6 months of HFC diet. METHODS AND RESULTS: Diet duration was correlated with a craniocaudal progression of lesion development and with an increase in severity of the lesion. Typically, the lesions contained smooth muscle cells, macrophages, and T lymphocytes and were covered by an intact endothelium. Whereas DNA synthesis (BrdU uptake) was usually elevated in type II lesions (8.6+/-0.8% versus 1.0+/-0.2% in the nondiseased arterial wall; P<0.05), apoptosis was found primarily in advanced lesions (type IV, 1.3+/-0.1% and type V, 1.2+/-0.2% versus 0.04+/-0.04% in the nondiseased arterial wall [P<0.05]). Cell phenotyping revealed that the majority of DNA synthesis and apoptosis was confined to the macrophage-derived foam cell (68.6+/-3. 0% and 82.2+/-4.6%, respectively). CONCLUSIONS: This study shows that in APOE*3-Leiden mice, duration of an HFC diet is associated with (1) a craniocaudal progression of lesion development and (2) an increased complexity of atherosclerotic lesions. Furthermore, DNA synthesis is predominant in early lesions, whereas apoptosis is present mainly in more advanced lesions. Both parameters of cell turnover are confined primarily to the macrophage-derived foam cell.     

Upper Limit Ventricular Stimulation in Respiratory Rate Responsive Pacing due to Electrocautery

Transient programmed upper limit stimulation (150 bpm) was observed during repetitively utilized electrocautery in the beginning of an open-heart surgical procedure in a patient with a minute ventilation rate responsive ventricular pacemaker. This tachycardia caused severe hemodynamic deterioration, and was also initiated by internal heart massage and manual ventilation. Considering the recommendations of the manufacturer, this series of serious events could have been prevented, when reprogramming to the inhibited mode had been executed in anticipation of the operation.     

Uptake of cationzied albumin coupled liposomes by cultured porcine brain microvessel endothelial cells and intact brain capillaries

The suitability of protein-coupled liposomes as drug carriers for brain specific targeting was investigated using albumin (BSA) and cationized albumin (CBSA), respectively, as model proteins. Liposomes coated with polyethylene glycol (sterically stabilized, PEG-liposomes) were prepared from phosphatidylcholine, cholesterol, and a PEG-derivatized phospholipid and covalently coupled to thiolated BSA or CBSA. Liposomes were loaded with carboxy-fluorescein and rhodamine-labeled dipalmitoyl-phosphatidylethanolamine as hydrophilic and lipophilic marker compounds, respectively. The interaction of these constructs with monolayers of porcine brain capillary endothelial cells (BCEC) and freshly isolated porcine brain capillaries was studied by means of fluorescence assays and confocal laser scanning fluorescence microscopy (CLSFM). In contrast to BSA, CBSA was rapidly taken up by cultured BCECs. BSA-coupled liposomes did not interact with endothelial cells, whereas CBSA-coupled liposomes bound to cellular surfaces and exhibited time dependently a high intracellular accumulation. CBSA-conjugated liposomes were also taken up by intact brain capillaries. Cellular uptake could be inhibited by free cationized albumin, phenylarsineoxide, nocodazole, and filipin, but not by dansylcadaverine, suggesting a caveolae-mediated incorporation process. Immunostaining demonstrated a high expression of caveolin in the capillary endothelium. In conclusion, liposomes coupled to CBSA are taken up into brain endothelium via an endocytotic pathway and may therefore be a suitable carrier for drug delivery to the brain.